Despite continuous attempts to improve therapy, the outcomes of acute myeloid leukemia remain almost unchanged over last decades. Drugs made with a more complete understanding of the biology of acute myeloid leukemia do not equal the hopes for better prognosis. The best results are achieved only with high-dose chemotherapy, which is only possible for a limited number of patients. High phenotypic and genotypic heterogeneity of acute myeloid leukemia defines the relevance to develop personalized approaches to therapy, including those based on determination of individual drug sensitivity of blast cells.This article presents the results of developing an ex-vivo model of acute myeloid leukemia, as well as testing of two in vitro sensitivity assessment methods: evaluation of the genotoxicity of drugs in the micronucleus test and vitality and sensitivity to chemotherapy in sorted blast cells. Prospects of individualized therapy of acute myeloid leukemia were determined based on introduction into clinical practice and continuing the research.
BACKGROUND: The most important cause of anemia in the world is iron deficiency. Young women are more susceptible to the formation of latent iron deficiency and iron deficiency anemia in comparison with other population groups. Iron deficiency conditions can lead to a deterioration in exercise tolerance and adaptation to them, however, the effect of latent iron deficiency and iron deficiency anemia on cognitive functions, emotional status and quality of life is still a subject of discussion, which may be due to the small number of studies in which iron deficiency conditions are studied in the absence of concomitant chronic diseases. AIM: Evaluate the effect of latent iron deficiency and iron deficiency anemia on the quality of life in young women. MATERIALS AND METHODS: a cross-sectional simultaneous study was conducted in women aged 1821 years. The occurrence of iron deficiency conditions was assessed, a study of the quality of life was conducted using the SF-36 questionnaire. In the statistical processing of the results obtained, the assessment of normality within each group was carried out using Shapiro-Wilk test. For an intergroup comparison of the results obtained between two independent groups, MannWhitney test was used, and Wilcoxon test was used when comparing the results of two dependent groups. The intergroup comparison between the three groups was carried out using KruskalWallis test. When detecting deviations from the null hypothesis, a posteriori analysis was carried out using MannWhitney test with Bonferroni correction. RESULTS: 68 subjects aged 1821 took part in the study. The median age was 18 years [18; 21]. 25 (36.7%) women were diagnosed with ID, 16 (23.5%) with IDA. The level of C-reactive protein in all subjects was 5 mg/l, median 2.4 [1.2; 3.1] mg/l. During a posteriori analysis, comparable indicators of the total blood count between the groups of healthy women and those with ID were revealed. At the same time, there were no differences in ferritin levels between the ID and IDA groups. In the study of quality of life, statistically significant intergroup differences between the study groups were obtained in the scales of general health, vital activity, role functioning due to emotional state, mental health and general mental well-being. When conducting a posteriori analysis, the number of points in the questionnaire scales turned out to be comparable between groups of healthy women and those with ID. CONCLUSIONS: data on the high incidence of latent iron deficiency and iron deficiency anemia in young women have been obtained. The presence of latent iron deficiency does not independently affect the quality of life associated with health. Mild iron deficiency anemia moderately reduces the quality of life due to the emotional component.
Background:This abstract presents the experience of cultivating the peripheral blast cells of a patient with resistant acute myeloid leukemia (AML) and testing 2 methods for assessing the effects of chemotherapy drugs on them.Aims:Suitability examination of cell sorting (CS) and micronucleus test (MT) for assessing the genotoxicity of chemotherapy drugs.Methods:Blast cells were obtained by taking blood from a patient with multi‐resistant AML. On sampling days, the percentage of blasts in the patient's peripheral blood ranged from 50% to 75%. In total, 3 in vitro experiments were conducted.In experiment №1, 520650 CD34+ cells were sorted into 2 tubes, which were incubated for 4 days (37 °C, 5% CO2) in 5 ml of complete nutrient medium (CM): 80% RPMI‐1640, 10% fetal calf serum, 10% of the patient's original serum, 10 μl of phytohaemagglutinin and 100 U/ml penicillin.After the first day, decitabine was added to one of the samples at a concentration of 1160 ng/ml. To assess the genotoxicity of the drug at the end of cultivation, we determined the number of cells that retained viability by evaluating the results of labeling free DNA.In experiments №2 and №3, 0.5 ml of blood was cultured with 5 ml of CM. After 24 hours, various concentrations of decitabine (290 ng/ml, 580 ng/ml, 1160 ng/ml) were added to the samples of experiment №2. Daunorubicin (3400 ng/ml) was added to the samples of experiment №3, as well as its combination with interferon alpha‐2a in the calculation of 3600 IU/ml. Next, samples were cultured for 48 hours. To assess the genotoxicity in these experiments MT was used.Results:The results of experiment №1 are presented in Figure 1, №2 in table 1, №3 in table 2.Summary/Conclusion:1. CS allows selection of the required number of cells with the required phenotype and assess their viability after cultivation with high accuracy. In the sample with the addition of decitabine, living blast cells turned out to be almost 2 times less than in the control sample.imageimage2. MT can be used to assess the genotoxicity of chemotherapy drugs for peripheral blood blast cells. From the results of experiment №2, it follows that the concentration of the drug has a direct correlation with the level of its genotoxicity on blast cells. In experiment №3, the combination of daunorubicin with interferon showed much stronger genotoxic effects on blast cells compared to daunorubicin without interferon.
Direct оral Anticoagulants (DOACs) include direct thrombin inhibitor (dabigatran) and factor X inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban). The) are widely used worldwide for the prevention and treatment of venous thrombosis. The popularity of DOACs is explained by convenient and predictable pharmacodynamics, the lack of need for regular monitoring of the therapeutic effect, as well as more predictable food-drug interaction and bioavailability. However, like any other anticoagulants, DOACs are characterized by an increased risk of bleeding, especially gastrointestinal one. The correct approach to the prescription of DOACs and prevention of bleeding during treatment including the intake of anticoagulants can significantly reduce the probability of life-threatening complications. In the case of bleeding, the use of specific and nonspecific DOACs antidotes is indicated. Significant bleeding requires the attending physician to know a clear course of action in accordance with published algorithms to save the patient’s life.
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